Back to Journals » International Journal of Nanomedicine » Volume 9 » Issue 1

Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line

Authors Yurgel VC, Oliveira CP, Begnini KR, Schultze E, Thurow HS, Leon PMM, Dellagostin OA, Campos VF, Beck RC, Guterres SS, Collares T, Pohlmann AR, Seixas FK

Received 24 October 2013

Accepted for publication 12 December 2013

Published 25 March 2014 Volume 2014:9(1) Pages 1583—1591

DOI https://doi.org/10.2147/IJN.S56506

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Virginia C Yurgel,1,* Catiuscia P Oliveira,2,* Karine R Begnini,1 Eduarda Schultze,1 Helena S Thurow,1 Priscila MM Leon,1 Odir A Dellagostin,1 Vinicius F Campos,1 Ruy CR Beck,2 Silvia S Guterres,2 Tiago Collares,1 Adriana R Pohlmann,2–4 Fabiana K Seixas1

1Programa de Pós-Graduação em Biotecnologia (PPGB), Grupo de Pesquisa em Oncologia Celular e Molecular, Laboratório de Genômica Funcional, Biotecnologia/Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 4Centro de Nanociência e Nanotecnologia, CNANO-UFRGS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

*These authors contributed equally to this work

Abstract: Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors.

Keywords: MTX derivative, resistance, apoptotic cell death, cell cycle arrest, nanocarriers, drug delivery, drug targeting

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model

Boechat AL, Oliveira CP, Tarragô AM, Costa AG, Malheiro A, Guterres SS, Pohlmann AR

International Journal of Nanomedicine 2015, 10:6603-6614

Published Date: 22 October 2015

Oxygen supersaturated fluid using fine micro/nanobubbles

Matsuki N, Ishikawa T, Ichiba S, Shiba N, Ujike Y, Yamaguchi T

International Journal of Nanomedicine 2014, 9:4495-4505

Published Date: 23 September 2014

Antibacterial properties of silver nanoparticles synthesized using Pulicaria glutinosa plant extract as a green bioreductant

Khan M, Khan ST, Khan M, Adil SF, Musarrat J, Al-Khedhairy AA, Al-Warthan A, Siddiqui MRH, Alkhathlan HZ

International Journal of Nanomedicine 2014, 9:3551-3565

Published Date: 28 July 2014

Enhanced oral absorption and therapeutic effect of acetylpuerarin based on D-α-tocopheryl polyethylene glycol 1000 succinate nanoemulsions

Sun DQ, Wei XB, Xue X, Fang ZJ, Ren MR, Lou HY, Zhang XM

International Journal of Nanomedicine 2014, 9:3413-3423

Published Date: 18 July 2014

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Li D, Yang K, Li JS, Ke XY, Duan Y, Du R, Song P, Yu KF, Ren W, Huang D, Li XH, Hu X, Zhang X, Zhang Q

International Journal of Nanomedicine 2012, 7:6105-6114

Published Date: 17 December 2012

Polyacrylonitrile nanofibers coated with silver nanoparticles using a modified coaxial electrospinning process

Yu DG, Zhou J, Chatterton NP, Li Y, Huang J, Wang X

International Journal of Nanomedicine 2012, 7:5725-5732

Published Date: 12 November 2012

Effects of oridonin nanosuspension on cell proliferation and apoptosis of human prostatic carcinoma PC-3 cell line

Zhen Zhang, Xiumei Zhang, Wei Xue, et al

International Journal of Nanomedicine 2010, 5:735-742

Published Date: 4 October 2010